Biomedical Engineering Reference
In-Depth Information
The resolution provided by a physical map depends on the methodology used to create the map. The
simplest form of physical mapping is cytogenic mapping, which is based on the banding of stained
chromosomes that is visible through light microscopy. Generally more useful in bioinformatics work is
high-resolution sequence-based physical mapping, which defines distances between markers and the
intervening sequence in terms of base pairs. One of the most popular sequence-based physical
mapping techniques uses sequence tagged sites (STSs), which are short, unique DNA sequences. A
common source of STSs are expressed sequence tags (ESTs), which are short sequences derived
from analysis of complementary DNA (cDNA). STSs can also be obtained by sequencing random
pieces of cloned DNA.
Some of the most valuable mapping techniques provide connections between physical and genetic
maps. The most common methods of identifying these connections involve radiation hybrid (RH)
mapping and simple sequence length polymorphisms (SSLPs). Radiation hybrid mapping, which can
be used to reveal the distance between genetic markers, is performed by exposing DNA to measured
doses of radiation, which causes the DNA to break up. By varying the amount of radiation, the
average distance between DNA sequence breaks can be modified. As a result, RH mapping can be
used to localize virtually any genetic marker. Another approach to linking genetic and physical maps
is based on SSLPs, which are arrays of repeat sequences that display length variations. Because
SSLPs can serve as both a genetic marker and as the basis for sequence mapping—a Rosetta Stone
of sorts—the technique is valuable in connecting physical and genetic maps.
The accuracy of the mapping process is highly dependent on computational methods used to
manipulate the data acquired by experimentation or modeling. The typical mapping process,
illustrated in
Figure 5-4
, involves an integration of several mapping approaches. Using link mapping,
the chromosome is cut into relatively large pieces, and markers are assigned in stages to make a
more detailed map. Cytogenic mapping is used to create a first-pass, a low-resolution chromosome
map that becomes more detailed as more marker data are collected and assigned to positions along
the chromosome.
Figure 5-4. Gene Mapping Processes. A variety of techniques are available
for creating physical and genetic maps.
